Investigating the Association Between ABO Blood Groups and Rhesus Factors with Dengue and Chikungunya Virus Infections During the 2017 Outbreak in Bangladesh

Introduction

Dengue and chikungunya viruses, transmitted by Aedes mosquitoes, pose health threats due to rapid transmission. Common symptoms, transmission, and prevalence in tropical areas hinder the diagnosis of both infections. Severe cases strain resources, underscoring the need for organized prevention, control, and awareness to handle outbreaks. Aedes mosquitoes, primarily vectors for these two viruses, prefer human blood for postmating meals. Some studies, although having some limitations, explored the link between ABO blood groups and dengue/chikungunya infections (Khode et al., 2013; Kumar et al., 2010; Lokireddy et al., 2009; Ravichandran et al., 2019).

ABO group and rhesus (Rh) factor are key factors in blood transfusion, extensively studied in genetics and disease susceptibility. Its impact spans immunology and vaccinology (Galhena et al., 2023; Huang et al., 2005; Lee et al., 2018; Pereira et al., 2022). Understanding dengue and chikungunya infection susceptibility and resistance is vital for innovative treatments, mosquito control, and vaccine development. Thus, this study aimed to investigate ABO groups and Rh factors during the 2017 dengue–chikungunya outbreak in Bangladesh.

Materials and Methods

This study was conducted at the Department of Virology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, during the dual dengue and chikungunya outbreak (March–September 2017). During the outbreaks, febrile participants provided 5 mL of venous blood for testing dengue NS1 antigen/dengue antibodies (IgM/IgG) and chikungunya IgM antibodies using immunochromatographic kits (SD Biosensor, South Korea). ABO and Rh blood grouping were performed on dengue- and chikungunya-positive patients.

The sample size for this study was calculated using the formula for case–control studies (Schlesselman and Stolley, 1982), considering the anticipated minimum odds ratio (OR) of 1.5, proportion of the general population with blood groups O (27.6%), A (23.5%), B (39.8%), and AB (9.2%) (Sultana et al., 2013); 5% level of significance, and 80% power. The minimum sample size calculated was 1028 for cases and 1028 for controls. However, since data of 1438 dengue cases, 1077 chikungunya cases, and 12,170 healthy blood donors from five different hospitals in Dhaka city were available, we included them in the analysis to enhance statistical power.

Descriptive statistics were generated to describe the distribution and rates of infection across blood groups. The study was approved by the institutional review board (IRB), BSMMU (BSMMU/6094). The risk of infection across groups was explored by fitting multivariable logistic regression models, using SPSS software ver. 22.0 (IBM, Armonk, NY).

Result

The study included data from 14,685 individuals—12,170 healthy blood donors, alongside 1438 and 1077 with dengue and chikungunya infections, respectively (Table 1). Age and gender distribution between the study groups was not significant (p > 0.5). A primary constraint of this study was the inability to include vector density and sociodemographic information. Susceptibility to dengue (67.29%) and chikungunya (68.43%) was higher in 18–49-year olds. The male population showed elevated dengue (58.90%) and chikungunya (56.17%) infection rates. Participants were categorized as A, B, O, or AB based on blood type antigens.

Among febrile patients, O blood type exhibited the highest dengue (47.5%) and chikungunya (49.3%) infection rates (total-48.27%). Conversely, the AB blood type had the lowest dengue (8.62%) and chikungunya (8.17%) infection rates (total 8.42%). Blood groups for 12,170 healthy donors were 24.63%, 32.24%, 30.32%, and 12.82% for A, B, O, and AB, respectively. The majority (99.43%) were Rh factor positive. Though only 69 (0.57%) were Rh factor negative among the general population, dengue and chikungunya infection was observed in 41 (2.85%) and 14 (1.3%) individuals with Rh factor negative, respectively (p < 0.05).

Combined infection odds were 2.0 (95% confidence interval [CI] 1.8, 2.4), 3.5 (95% CI 3.0, 4.0), and 1.4 (95% CI 1.1, 1.7) times higher in groups B, O, and AB than in group A. Blood group A had lower susceptibility. Rh negative factor group had 4.2 times higher odds (95% CI 2.9, 6.0) than Rh positive group. When the OR of having each of the infections was considered separately, blood groups O and A remained relatively more and less prone to both of the infections, respectively. All these odds values were statistically significant; the p-value varied from <0.05 to 0.001.

Discussion

This study observed that blood group O has a higher relative risk of dengue and chikungunya virus infections, whereas blood group A displays reduced susceptibility. About 50% of dengue or chikungunya patients had O positive blood group, compared with 9% with blood group AB. Although infection among blood group A patients was higher (11%), the OR of blood group A had the lowest infection risk, that is, susceptibility. This is because, in comparison with the number of healthy blood donors with blood groups A and AB, blood group A exhibited a lower attack rate (9.9%) than the blood group AB (13.6%) (data not shown).

Conversely, individuals with blood group O are 3.5 times more susceptible to both infections compared with individuals with blood group A. Many studies exploring the association of ABO blood groups with dengue or chikungunya infections reported a higher prevalence among blood group O (Khode et al., 2013; Kumar et al., 2010; Lokireddy et al., 2009; Ravichandran et al., 2019), but were limited by overlooking general population blood group data during comparisons.

Interestingly, this study, even after incorporating the general population as a control, still found individuals with blood group O to be predominant in both infection types. Considering general people blood group data as control, an association of blood group AB with dengue fever (DF)/dengue hemorrhagic fever (DHF) development was reported in patients from Jaffna, Sri Lanka (Murugananthan et al., 2018), which is diverging from most studies, including this study. Contrary to the findings of Murugananthan et al., a different study carried out in Sri Lanka's Western Province found that O+ persons made up the main DF/DHF-infected group in 2017 and 2018 (Galhena et al., 2023).

The higher susceptibility of blood group O and the low susceptibility of blood group A observed in this study align with Aedes mosquito preferences observed in prior studies conducted on laboratory-reared mosquitoes. It was observed that Aedes albopictus has preferences as O>B/AB>A, and landing preference as O>B/AB>A with significantly more landings on individuals of blood group O (Shirai et al., 2004). Similarly, Galhena et al. (2023) noted that the Aedes aegypti blood group favored as O−> O+ > A−> A+, which supports the findings of this study, including the susceptibility associated with Rh-negative blood groups.

ABO blood groups exhibit connections not only with dengue and chikungunya virus infections, but also with other viruses such as influenza, hepatitis B, and SARS-CoV-2 and altered responses to vaccines (Pereira et al., 2022). It indicates that besides vector preferences, other underlying mechanisms are at play. Norwalk virus specifically targets the A antigen present in red blood cells, making blood group A more susceptible (Huang et al., 2005). Furthermore, blood group antigens influence the effectiveness of rotavirus vaccines (Lee et al., 2018).

Currently, several dengue and chikungunya vaccines are either available for administration or are in development stages. Although more research is required to establish such relative vulnerability or resistance to both of the infections, the effectiveness of dengue and chikungunya vaccines against different blood groups requires additional focused investigations.